Genetic Testing

​People can eat healthy, exercise, and maintain a healthy weight but still carry genetic risk factors that put them at increased risk of disease. However, knowing your genetic makeup can help guide lifestyle and medication choices that improve the opportunity for a long healthy life. Our genetic make-up influences our health risk, but it does not have to be our destiny - there are things we can do to prevent activating bad genes for cancer or heart disease. 

1. Apolipoprotein E

Apo E is a critical protein that acts like a taxi for fats and cholesterol in our body, delivering vital nutrients that help form new cell membranes, hormones, and much more. We inherit one allele (one half) of the gene from each parent. Though each person has two Apo E numbers, people are typically categorized as a 2, 3, or 4.
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Knowing a patient’s Apo E genotype allows the practitioner to individualize diet, lifestyle, and cholesterol lowering protocols in order to ultimately decrease the patient’s risk of cardiovascular and neurodegenerative disease. What is efficacious for one patient may not be beneficial for another, so this information allows for customizable treatment regimens.

2. Kif6 (Kinesin Family Member 6)

This test identifies individuals with the Kif6 gene variant, which is correlated with an increased risk of coronary heart disease (CHD). However, statin therapy greatly diminishes this CV risk in the patients with this gene, so statins are important to consider in this patient population.

This genetic test determines whether an individual has the KIF6 variant rs20455. This variant increases CHD risk by about 1.5 fold, but some studies have shown that this risk can be normalized with statin therapy. In both the CARE and WOSCOPS trials, Pravastatin helped lower CV risk in Kif6 carriers, but not in non-carriers. 1 Similarly, in the PROVE IT trial, carriers of the Kif6 risk allele received significant risk reduction from atorvastatin, more so than non-carriers. On the other hand, in the Heart Protection Study and Jupiter trial, Kif6 did not predict statin response (no difference was seen). 3 4
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In some studies, KIF6 carriers experienced a 13% greater reduction in CHD per mmol/L decrease in LDL cholesterol than non-carriers. The difference in clinical benefit may be due to the increased vulnerability to LDL cholesterol among KIF6 carriers. This reduction could explain the clinical benefit seen among KIF6 carriers and non-carriers (regarding statin therapies that lower LDL cholesterol). 2

​Take home message: Kif6 positive patients may have a higher lifetime risk of cardiovascular disease, but in these patients, any statin will help lower their risk. Alternately, Kif6 negative patients can still be at risk, but they may not benefit from atorvastatin or pravastatin, so a different statin should be considered in these patients.

3. 9p21 CVD Risk Genotype Test – “The Heart Attack Gene”

This genetic test helps identify individuals who may be at an increased risk of premature cardiovascular disease. Knowing this information can help the medical provider classify the patient’s cardiovascular risk more accurately, and implement more aggressive management of modifiable risk factors in appropriate patients.

The 9p21 gene has been shown to be an independent predictor of cardiovascular risk. Carriers have a 1.5-2.0 fold increased risk of cardiovascular disease (particularly stroke and abdominal aortic aneurysm) compared to non-carriers.
There are two possible 9p21 haplotypes, but each type confers a different type of cardiovascular risk.

a) Haplotype rs1333049 is associated with more severe multi-vessel obstructive coronary artery disease, though it is not associated with as many heart attacks.
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b) Haplotype rs518394, on the other hand, is associated with prevalent heart attacks, but without significant stenosis (obstruction) of coronary arteries.

4. 4q25 Atrial Fibrillation Risk Genotype Test

This test identifies individuals with an increased genetic risk of developing atrial fibrillation (Afib). Atrial fibrillation is a potential dangerous arrhythmia of the heart that can increase a patient’s risk of forming blood clots that can cause a stroke.

Patients who are positive for 4q25, but who already have Afib, may not respond well to ablation therapy . . . so this test helps differentiate who might be a better candidate for management with medication. 

5. CYP2C19 (Plavix test)

The cytochrome P450 (CYP) enzyme 2C19 is found in the liver - it converts the pro-drug clopidogrel (Plavix) into its active form. The CYP2C19 test assesses how well a patient metabolizes clopidogrel. Impaired metabolism of clopidogrel could lead to increased risk of clotting and stent closure, or alternately, to significant bleeding. So this test plays an important role in aiding treatment decisions regarding anticoagulant therapy (for patients in need of prescription blood thinners).

6. Haptoglobin

This blood test analyzes your haptoglobin (Hg) genotype, offering insight into your risk for heart disease and which diet and supplements would be most beneficial for you. If you have diabetes, you can not only find out if you have a genotype that raises heart disease risk as much as smoking does, but if you have this high-risk genotype, research suggests that you can almost entirely eliminate this excess risk by taking an inexpensive vitamin.

If you’re not diabetic, you can find out if you have a genotype linked to increased risk for intestinal, autoimmune and inflammatory disorders and if you’d benefit from a gluten-free diet and probiotics.

The Hg gene has two alleles (Hg 1 and Hg 2), resulting in 3 possible genotypes: Hg 1-1 (low risk), Hg 1-2 (intermediate risk) and Hg 2-2 (high risk). Diabetics with Hp 2-2 genotype are five times more likely to develop heart disease than those with the Hp 1-1 genotype! The good news, however, is that randomized studies show that taking 400 i.u. of vitamin E daily counteracts this increased risk in people with diabetes.

While you might wonder if all diabetics should take vitamin E–and skip the gene test–research shows that for most people, vitamin E supplements raise risk for heart attacks and early death from cardiovascular disease. The only people who benefit from this supplement are diabetics with the Hg 2-2 genotype.
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There is also recent evidence that both diabetic and non-diabetic people with the Hp 1-2 or Hp 2-2 genotypes do best if they follow a gluten-free diet and take a daily probiotic supplement. Before taking any dietary supplement, discuss the pros and cons with your doctor and ask if it’s appropriate for you.